World Journal of Surgery

, Volume 32, Issue 8, pp 1757–1762 | Cite as

Preoperative Neutrophil-to-Lymphocyte Ratio as a Prognostic Predictor after Curative Resection for Hepatocellular Carcinoma

  • D. Gomez
  • S. Farid
  • H. Z. Malik
  • A. L. Young
  • G. J. Toogood
  • J. P. A. Lodge
  • K. R. Prasad



This study was designed to evaluate the impact of an elevated preoperative neutrophil-to-lymphocyte ratio (NLR) on outcome after curative resection for hepatocellular carcinoma (HCC).


Patients undergoing resection for HCC from January 1994 to May 2007 were identified from the hepatobiliary database. Demographics, laboratory analyses, and histopathology data were analyzed.


A total of 96 patients were identified with a median age at diagnosis of 65 (range, 15–85) years. The 1-, 3-, and 5-year overall survival rates were 80%, 58%, and 52%, respectively. Although the presence of microvascular invasion, NLR ≥5, and R1 resection margin were adverse predictors of overall survival, there were no independent predictors identified on multivariate analysis. The 1-, 3-, and 5-year disease-free survival rates were 74%, 63%, and 57%, respectively. Preoperative tumor biopsy, NLR ≥ 5, multiple liver tumors, microvascular invasion, and R1 resection margin were all predictors of poorer disease-free survival. Multivariate analysis showed that a NLR ≥ 5 and R1 resection margin were independent predictors of poorer disease-free survival. The median disease-free survival of those with a NLR ≥ 5 was 8 months compared with 18 months for those with a NLR < 5.


Preoperative NLR ≥ 5 was an adverse predictor of disease-free and overall survival.


Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and its prevalence is increasing because of the increase in chronic hepatitis infection [1]. Hepatic resection can potentially provide 5-year survival rates up to 70% in selected patients [2]. The recently published American Association for the Study of Liver Diseases guidelines [3] have suggested that liver resection should be the treatment of choice for solitary lesions that arise in noncirrhotic livers and in patients with Child-Pugh grade A cirrhosis who have well-preserved liver function. Besides recognized adverse prognostic factors, such as large tumor size [4, 5], multifocal disease [6, 7], and vascular invasion [6, 8], there is increasing evidence that correlates the presence of systemic inflammation with poorer cancer-specific survival in certain tumors [9, 10]. Current understanding suggest that the host’s inflammatory response to tumor and/or the systemic effects exerted by the tumor leads to up-regulation of the inflammatory process, predisposes the tumor to proliferate and metastasize through the inhibition of apoptosis, promotion of angiogenesis, and damage of DNA [9, 11, 12].

The presence of a systemic inflammatory response can be determined by both the expression of C-reactive protein (CRP) [13] and an elevation in neutrophil-to-lymphocyte ratio (NLR) [14]. Hashimoto et al. [15] showed that an elevated preoperative CRP was associated with early recurrence and poorer survival after resection for HCC. Similar findings have been observed in cases of colorectal cancer [16]. Although an elevated CRP has been widely used in this respect, not all centers routinely measure preoperative CRP. An elevation in NLR, another marker of inflammation, has been shown to be associated with poorer prognosis in patients with cardiovascular and peripheralvascular disease [14, 17], colorectal carcinoma [18], and more recently, colorectal liver metastases [19]. These studies have focused on the preinterventional or surgical profile of NLR as it reflects the inflammatory status of the patient before treatment. Although the white cell and differential counts may vary at different periods, a preoperatively high ratio of 5:1 is most likely to reflect aggressive disease and hence, poorer outcome.

This study was designed to evaluate the impact of systemic inflammation, represented by an elevated preoperative NLR, on outcome after potentially curative hepatic resection for HCC.

Materials and methods


Patients with HCC undergoing hepatic resection at the Hepatobiliary and Transplantation Unit, St. James’s University Hospital (SJUH), Leeds, United Kingdom, during the 13-year period from January 1994 to May 2007 were identified from a prospectively maintained hepatobiliary database.

Demographic, clinical, and laboratory data, including patient age, sex, white cell and differential counts, tumor markers [alpha (α)-fetoprotein], and presenting features were recorded. All white cell and differential counts were taken on the day before surgery, and none of the patients had clinical symptoms or signs of sepsis. The NLR was calculated from the differential count by dividing the absolute neutrophil count by the absolute lymphocyte count. NLR ≥ 5 was considered raised in accordance with published literature [18]. Preoperative radiological assessments included a thoracic, abdomen and pelvis computed tomography (CT), isotope bone scan, and magnetic resonance imaging (MRI) of the liver.


Hepatic parenchymal transection was performed by using the Cavi-Pulse Ultrasonic Surgical Aspirator (CUSA, Model 200T, Valley Lab., Boulder, CO). The number of hepatic (Couinaud’s) segments resected was determined by the procedure performed as stated in the Brisbane nomenclature [20]. In certain cases, an intermittent Pringle maneuver was used, consisting of repeated cycles of 15 minutes of ischemia followed by 5 minutes of reperfusion. Intraoperative ultrasound was performed to confirm the findings of preoperative imaging and to assist in surgical planning. Resection and reconstruction of the portal vein and inferior vena cava also was performed when the tumor was judged to have invaded the vasculature. A major resection was defined as resection of three or more segments. In cases in which multiple resections were performed at a single setting, the most extensive resection was considered the main procedure.

The postoperative data collated included complications, clinical outcome (morbidity and mortality), and histopathological information regarding the resected specimens. Patients who developed evidence of encephalopathy or became jaundiced, with coagulopathy after surgery, were considered as having developed significant transient liver failure. Perioperative mortality included all deaths within 30 days of surgery. Transfusion of blood products (packed red cells or whole blood) during surgery or in-hospital stay after surgery also was recorded.


Patients were followed up at specialist hepatobiliary clinics. An intensive policy of postoperative surveillance is practiced within this unit, and no patients were lost to follow-up. Patients have three monthly thoracic and abdominal CT performed during the first postoperative year, followed by six monthly during the second year. In the following three years (years 3–5), an annual CT scan was performed, and finally at years 7 to 10 of follow-up. In addition, liver MRI was used to define suspicious lesions demonstrated on CT and/or raised α-fetoprotein. Overall and disease-free survival data were recorded.

Statistical analysis

Categorical data were presented as frequency and were analyzed by using the Pearson’s chi-squared test. The Kaplan-Meier method was used to assess the actuarial survival and disease recurrence rate. Univariate analysis was performed to assess for a significant difference in clinicopathological characteristics that influenced overall and disease-free survival after curative resection. A multivariate analysis was performed by Cox regression (step-wise forward model) for variables significant on univariate analysis. All statistical analyses were performed by using the SPSS® for Windows™ version 15.0 (SPSS Inc., Chicago, IL), and statistical significance was taken at the 5% level.


Demographic data

During the study period, 96 patients underwent potentially curative resection for HCC. The median age at diagnosis was 65 (range, 15–85) years, and there were 72 men and 24 women. The most common mode of presentation was abdominal pain in 25 patients followed by malaise and weight loss in 10 patients. Preoperative α-fetoprotein was raised in 27 patients. The NLR was elevated at ≥5 in 26 patients before surgery.

Surgical procedures

The commonest type of resection performed was right trisectionectomy in 25 patients, followed by right hemihepatectomy performed in 19 patients (Table 1). In addition, nine patients had vascular reconstruction (of which 2 had ex vivo resection), eight patients had tumor thrombectomy, eight patients required additional nonanatomical resection, and five patients required diaphragmatic resection.
Table 1

Operative data of patients in this study

Operative data (n = 96)

Left hemihepatectomy (resection of segments 2, 3, 4 ± 1)


Right hemihepatectomy (resection of segments 5, 6, 7, 8 ± 1)


Left trisectionectomy (resection of segments 2, 3, 4, 5, 8 ± 1)


Right trisectionectomy (resection of segments 4, 5, 6, 7, 8 ± 1)


Bisegmentectomy (resection of 2 segments)


Nonanatomical liver resection


The overall morbidity was 41% and there were two in-hospital deaths. The most common complication was intra-abdominal sepsis (n = 9), followed by wound infection in five patients. Five patients developed liver insufficiency postoperatively and transient renal failure was reported in four patients.


The majority of tumors were 5 cm or larger in maximum diameter (n = 73). The tumor was multiple in 33 cases. There were 24 cases with microscopic evidence of tumor at the resection margin. Microvascular infiltration was detected in 50 cases. Fourteen patients had underlying cirrhosis.

Overall and disease-free survival

At present, 60 patients are alive at a median follow-up of 30 (range, 6–152) months. Recurrent disease was reported in 29 patients during the follow-up period.

The 1-, 3-, and 5-year overall survival rates were 80%, 58%, and 52%, respectively. There were several demographic, clinical, and histopathological factors associated with worse overall survival based on univariate analysis (Table 2). The presence of microvascular infiltration (P = 0.04), NLR ≥ 5 (P = 0.03), and R1 resection margin (P < 0.01) were associated with significantly poorer overall survival. On multivariate analysis, there were no independent predictors of overall survival identified.
Table 2

Univariate analysis of overall and disease-free survival

Clinical variables

P value

Disease-free survival

Overall survival

Age ≥ 65 years



Gender (male)



Biopsy of tumor



AFP (>100)



Viral hepatitis (B or C)



Elevated NLR



Major hepatic resection



Blood transfusion



Multiple (>1) tumors



Large tumor size (>50 mm)



Macroscopic vascular invasion



Microscopic vascular invasion



Normal liver parenchyma



Presence of cirrhosis



Positive resection margin



AFP Alpha fetoprotein; NLR neutrophil-to-lymphocyte ratio

The 1-, 3-, and 5-year disease-free survival rates were 74%, 63%, and 57%, respectively. Preoperative biopsy of the tumor (P = 0.03), NLR ≥ 5 (P < 0.01), multiple liver tumors (P < 0.01), microscopic vascular invasion (P = 0.04), and evidence of tumor at the resection margin (P < 0.01) were all predictors of poorer disease-free survival. Multivariate analysis showed that a NLR ≥ 5 and tumor involvement at the resection margin were independent predictors of poorer disease-free survival (Table 3). The median disease-free survival of those with a NLR ≥ 5 was 8 (range, 3–56) months compared with 18 (range, 3–152) months for those with a NLR < 5 (P < 0.01; Fig. 1). In addition, patients with a NLR ≥ 5 were more likely to have background cirrhotic liver parenchyma (P = 0.04; Table 4).
Table 3

Multivariate analysis of variables influencing disease-free survival

Clinical variables for disease-free survival

Multivariate analysis

Risk ratio

Confidence interval

Biopsy of tumor




NLR ≥ 5




Multiple (>1) tumors




Macroscopic vascular invasion




R1 resection margin




NLR neutrophil-to-lymphocyte ratio

Fig. 1

Disease-free survival stratified by neutrophil to lymphocyte ratio. NLR neutrophil-to-lymphocyte ratio

Table 4

Univariate analysis of clinical and histopathology data comparing a neutrophil-to-lymphocyte ratio of <5 to ≥5

Clinical/histopathology data

NLR < 5 (n = 70)

NLR ≥ 5 (n = 26)

P value

AFP (>100)




Viral hepatitis (B or C)




Normal liver parenchyma




Presence of cirrhosis




Multiple (>1) tumors and/or large tumor size (>50 mm)




Microscopic and/or macroscopic vascular invasion




AFP Alpha fetoprotein; NLR neutrophil-to-lymphocyte ratio


The presence of an association between systemic inflammation and poorer prognosis has been established for a number of tumors, especially in cases of colorectal carcinoma [10, 13, 16, 21]. Besides applying raised CRP as a marker of inflammation known to be of prognostic value in patients with colorectal carcinoma [10, 13], the presence of an elevated preoperative NLR also has been validated as a marker of inflammation and shown to be of prognostic significance in colorectal carcinoma [18]. In the present study, NLR was selected as a marker for inflammation to be assessed, because patients treated within the institution did not routinely have CRP measured preoperatively. The current series recorded an elevation in NLR in 27% of patients undergoing liver resection for HCC. This prevalence is similar to that of patients with colorectal liver metastases treated within the institution with regards to inflammatory markers, including CRP [21] and NLR [19].

In the present series, poor prognostic indicators influencing overall survival included: preoperative NLR ≥ 5; microvascular invasion; and R1 resection margin. These patients had poorer overall survival on univariate analysis, although none of these factors were identified as independent predictors on multivariate analysis. With respect to disease-free survival, both preoperative NLR ≥ 5 and R1 resection margin were independent adverse predictors on multivariate analysis. This is the first study to implicate the relationship of an elevated preoperative NLR and a poorer prognosis for patients undergoing potentially curative liver resection for HCC. This association was present for both disease-free and overall survival. Because of the retrospective nature of this study and limited by the small sample size, further larger, prospective studies are required to validate this finding. In addition, there is a potential for the NLR profile to be used as a marker of disease response to treatment and recurrence. Studies assessing the correlation of serial levels of NLR before and after resection and at follow-up with recurrent disease and response to treatment are needed.

In addition, the current multivariate analysis also identified the status of the resection margin as a predictor of disease-free outcome. The institution has recently published its experience after resection of large HCC in 85 patients and showed adverse prognostic factors that influenced disease-free survival included R1 resection margin, multiple tumors, vascular invasion and preoperative tumor biopsy [22]. The addition of an inflammatory response, represented by NLR, in a slightly larger series of 96 patients with updated follow-up, has decreased the influence of all the other variables except resection margin as independent adverse predictors. Other authors have identified vascular involvement [4, 8, 23, 24], larger tumor size [4, 25], number of tumors [26, 27], resection margin status [28], Child Pugh status [28], HCC type [7, 29], underlying cirrhosis [30], extent of resection [8, 31], and blood loss or transfusion [8, 32] as prognostic predictors for patients after liver resection for HCC. The small sample size of the present study may be the limiting factor that other clinicopathological factors did not have a significant impact on outcome after resection. Although an association has been identified between an elevated preoperative NLR and poorer outcome, patients who express such a response should still be considered for curative resection due to the limited therapeutic alternatives to resection that provide good long-term survival.

The present series also noted an association between the presence of an elevated NLR ≥ 5 and the presence of underlying cirrhotic liver parenchyma. However, other histopathological features were not significantly different between the two NLR groups. This could be explained by the fact that a high ratio of 5:1 was chosen as a cutoff because this value has already been validated in patients with colorectal cancer. Furthermore, the present finding requires further validation in a larger series of patients.

The association between elevated NLR and poor prognosis is complex and remains to be elucidated. One possible explanation is the host’s immune response to tumor is lymphocyte dependent. Several studies on patients with colorectal carcinoma and its corresponding metastases have demonstrated that patients with weaker lymphocytic infiltration at tumor margins have a worse prognosis [33, 34]. Hence, patients with an elevated NLR have a relative lymphocytopenia, and this may result in exhibiting a poorer lymphocyte mediated immune response to malignancy, thereby worsening their prognosis and increasing the risk of tumor recurrence. Another possible explanation is that a raised neutrophil count may aid in the development and progression of the neoplasm by providing an adequate environment for growth and proliferation. Circulating neutrophils are known to contain and secrete the majority of circulating vascular endothelial growth factor (VEGF), a proangiogenic factor that is thought to be involved in tumor development [35]. This angiogenic activity has been associated with poor prognosis, as demonstrated in patients with gastric carcinoma [36, 37]. Recently, Park et al. showed that a strong VEGF-C (member of the VEGF family) expression on surgical specimens of intrahepatic cholangiocarcinoma significantly correlated with lymph node metastasis and was an independent predictor of a poorer prognosis [38]. Because both NLR and CRP are markers of systemic inflammation, there is likely to be an association between NLR and CRP as similar effects are seen when raised. Xavier et al. [39] observed an increase in serum levels of VEGF in the presence of raised CRP concentrations. In addition, Canna et al. [40] observed an inverse correlation between CRP levels and tumor lymphocytic infiltration, with a raised CRP concentration indicative of a weak infiltration of lymphocytes at the periphery of the tumor. Patients with a raised NLR have a relative lymphocytopenia, and this may result in exhibiting a weaker lymphocyte-mediated immune response to the tumor, thereby worsening their prognosis.

The preoperative inflammatory status of patients with HCC, represented by NLR, could be potentially a valuable prognostic predictor in directing both preoperative and postoperative therapies to these patients to improve their survival outcome. Currently, there are no specific therapeutic modalities available for patients who express tumor-related inflammatory responses, although the antiangiogenic activities of cyclooxygenase-2 inhibitors [41, 42] and vaccines that promote lymphocyte response to tumor [43] are being evaluated. Further understanding in this area is required, which may lead to the development of preoperative therapeutic targets that influence the expression of tumor-related inflammatory responses, and this may improve survival outcomes after resection for HCC.


The presence of an elevated preoperative NLR has been identified as an adverse predictor of outcome in patients undergoing potentially curative resection for HCC. Patients with high preoperative NLR should be considered as candidates for additional therapies after resection.


  1. 1.
    El-Serag HB, Mason AC (1999) Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med 340:745–750PubMedCrossRefGoogle Scholar
  2. 2.
    Llovet JM, Schwartz M, Mazzaferro V (2005) Resection and liver transplantation for hepatocellular carcinoma. Semin Liver Dis 25:181–200PubMedCrossRefGoogle Scholar
  3. 3.
    Bruix J, Sherman M (2005) Management of hepatocellular carcinoma. Hepatology 42:1208–1236PubMedCrossRefGoogle Scholar
  4. 4.
    Yeh CN, Chen MF, Lee WC, Jeng LB (2002) Prognostic factors of hepatic resection for hepatocellular carcinoma with cirrhosis: univariate and multivariate analysis. J Surg Oncol 81:195–202PubMedCrossRefGoogle Scholar
  5. 5.
    Regimbeau JM, Abdalla EK, Vauthey JN, Lauwers GY, Durand F, Nagorney DM, Ikai I, Yamaoka Y, Belghiti J (2004) Risk factors for early death due to recurrence after liver resection for hepatocellular carcinoma: results of a multicenter study. J Surg Oncol 85:36–41PubMedCrossRefGoogle Scholar
  6. 6.
    Grazi GL, Cescon M, Ravaioli M, Ercolani G, Gardini A, Del Gaudio M, Vetrone G, Cavallari A (2003) Liver resection for hepatocellular carcinoma in cirrhotics and noncirrhotics. Evaluation of clinicopathologic features and comparison of risk factors for long-term survival and tumour recurrence in a single centre. Aliment Pharmacol Ther 17(Suppl 2):119–129PubMedCrossRefGoogle Scholar
  7. 7.
    Llovet JM, Fuster J, Bruix J (1999) Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 30:1434–1440PubMedCrossRefGoogle Scholar
  8. 8.
    Nagasue N, Ono T, Yamanoi A, Kohno H, El-Assal ON, Taniura H, Uchida M (2001) Prognostic factors and survival after hepatic resection for hepatocellular carcinoma without cirrhosis. Br J Surg 88:515–522PubMedCrossRefGoogle Scholar
  9. 9.
    Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867PubMedCrossRefGoogle Scholar
  10. 10.
    Gunter MJ, Stolzenberg-Solomon R, Cross AJ, Leitzmann MF, Weinstein S, Wood RJ, Virtamo J, Taylor PR, Albanes D, Sinha R (2006) A prospective study of serum C-reactive protein and colorectal cancer risk in men. Cancer Res 66:2483–2487PubMedCrossRefGoogle Scholar
  11. 11.
    Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357:539–545PubMedCrossRefGoogle Scholar
  12. 12.
    Jaiswal M, LaRusso NF, Burgart LJ, Gores GJ (2000) Inflammatory cytokines induce DNA damage and inhibit DNA repair in cholangiocarcinoma cells by a nitric oxide-dependent mechanism. Cancer Res 60:184–190PubMedGoogle Scholar
  13. 13.
    McMillan DC, Canna K, McArdle CS (2003) Systemic inflammatory response predicts survival following curative resection of colorectal cancer. Br J Surg 90:215–219PubMedCrossRefGoogle Scholar
  14. 14.
    Zahorec R (2001) Ratio of neutrophil to lymphocyte counts–rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy 102:5–14PubMedGoogle Scholar
  15. 15.
    Hashimoto K, Ikeda Y, Korenaga D, Tanoue K, Hamatake M, Kawasaki K, Yamaoka T, Iwatani Y, Akazawa K, Takenaka K (2005) The impact of preoperative serum C-reactive protein on the prognosis of patients with hepatocellular carcinoma. Cancer 103:1856–1864PubMedCrossRefGoogle Scholar
  16. 16.
    McMillan DC, Wotherspoon HA, Fearon KC, Sturgeon C, Cooke TG, McArdle CS (1995) A prospective study of tumor recurrence and the acute-phase response after apparently curative colorectal cancer surgery. Am J Surg 170:319–322PubMedCrossRefGoogle Scholar
  17. 17.
    Duffy BK, Gurm HS, Rajagopal V, Gupta R, Ellis SG, Bhatt DL (2006) Usefulness of an elevated neutrophil to lymphocyte ratio in predicting long-term mortality after percutaneous coronary intervention. Am J Cardiol 97:993–996PubMedCrossRefGoogle Scholar
  18. 18.
    Walsh SR, Cook EJ, Goulder F, Justin TA, Keeling NJ (2005) Neutrophil-lymphocyte ratio as a prognostic factor in colorectal cancer. J Surg Oncol 91:181–184PubMedCrossRefGoogle Scholar
  19. 19.
    Halazun KJ, Aldoori A, Malik HZ, Al-Mukhtar A, Prasad KR, Toogood GJ, Lodge JP (2008) Elevated preoperative neutrophil to lymphocyte ratio predicts survival following hepatic resection for colorectal liver metastases. Eur J Surg Oncol 34:55–60PubMedGoogle Scholar
  20. 20.
    Strasberg SM (2005) Nomenclature of hepatic anatomy and resections: a review of the Brisbane 2000 system. J Hepatobiliary Pancreat Surg 12:351–355PubMedCrossRefGoogle Scholar
  21. 21.
    Wong VK, Malik HZ, Hamady ZZ, Al-Mukhtar A, Gomez D, Prasad KR, Toogood GJ, Lodge JP (2007) C-reactive protein as a predictor of prognosis following curative resection for colorectal liver metastases. Br J Cancer 96:222–225PubMedCrossRefGoogle Scholar
  22. 22.
    Young AL, Malik HZ, Abu-Hilal M, Guthrie JA, Wyatt J, Prasad KR, Toogood GJ, Lodge JP (2007) Large hepatocellular carcinoma: time to stop preoperative biopsy. J Am Coll Surg 205:453–462PubMedCrossRefGoogle Scholar
  23. 23.
    Vauthey JN, Klimstra D, Franceschi D, Tao Y, Fortner J, Blumgart L, Brennan M (1995) Factors affecting long-term outcome after hepatic resection for hepatocellular carcinoma. Am J Surg 169:28–35PubMedCrossRefGoogle Scholar
  24. 24.
    Lang H, Sotiropoulos GC, Domland M, Fruhauf NR, Paul A, Husing J, Malago M, Broelsch CE (2005) Liver resection for hepatocellular carcinoma in non-cirrhotic liver without underlying viral hepatitis. Br J Surg 92:198–202PubMedCrossRefGoogle Scholar
  25. 25.
    Lee NH, Chau GY, Lui WY, King KL, Tsay SH, Wu CW (1998) Surgical treatment and outcome in patients with a hepatocellular carcinoma greater than 10 cm in diameter. Br J Surg 85:1654–1657PubMedCrossRefGoogle Scholar
  26. 26.
    Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH (1999) Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg 230:309–321PubMedCrossRefGoogle Scholar
  27. 27.
    Ercolani G, Grazi GL, Ravaioli M, Del Gaudio M, Gardini A, Cescon M, Varotti G, Cetta F, Cavallari A (2003) Liver resection for hepatocellular carcinoma on cirrhosis: univariate and multivariate analysis of risk factors for intrahepatic recurrence. Ann Surg 237:536–543PubMedCrossRefGoogle Scholar
  28. 28.
    Lise M, Bacchetti S, Da Pian P, Nitti D, Pilati PL, Pigato P (1998) Prognostic factors affecting long term outcome after liver resection for hepatocellular carcinoma: results in a series of 100 Italian patients. Cancer 82:1028–1036PubMedCrossRefGoogle Scholar
  29. 29.
    Takayama T, Makuuchi M, Hirohashi S, Sakamoto M, Yamamoto J, Shimada K, Kosuge T, Okada S, Takayasu K, Yamasaki S (1998) Early hepatocellular carcinoma as an entity with a high rate of surgical cure. Hepatology 28:1241–1246PubMedCrossRefGoogle Scholar
  30. 30.
    Poon RT, Fan ST, Lo CM, Liu CL, Wong J (2002) Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation. Ann Surg 235:373–382PubMedCrossRefGoogle Scholar
  31. 31.
    Ziparo V, Balducci G, Lucandri G, Mercantini P, Di Giacomo G, Fernandes E (2002) Indications and results of resection for hepatocellular carcinoma. Eur J Surg Oncol 28:723–728PubMedCrossRefGoogle Scholar
  32. 32.
    Poon RT, Fan ST, Lo CM, Ng IO, Liu CL, Lam CM, Wong J (2001). Improving survival results after resection of hepatocellular carcinoma: a prospective study of 377 patients over 10 years. Ann Surg 234:63–70PubMedCrossRefGoogle Scholar
  33. 33.
    Svennevig JL, Lunde OC, Holter J, Bjorgsvik D (1984) Lymphoid infiltration and prognosis in colorectal carcinoma. Br J Cancer 49:375–377PubMedGoogle Scholar
  34. 34.
    Okano K, Maeba T, Moroguchi A, Ishimura K, Karasawa Y, Izuishi K, Goda F, Usuki H, Wakabayashi H, Maeta H (2003) Lymphocytic infiltration surrounding liver metastases from colorectal cancer. J Surg Oncol 82:28–33PubMedCrossRefGoogle Scholar
  35. 35.
    Kusumanto YH, Dam WA, Hospers GA, Meijer C, Mulder NH (2003) Platelets and granulocytes, in particular the neutrophils, form important compartments for circulating vascular endothelial growth factor. Angiogenesis 6:283–287PubMedCrossRefGoogle Scholar
  36. 36.
    Fondevila C, Metges JP, Fuster J, Grau JJ, Palacin A, Castells A, Volant A, Pera M (2004) p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer. Br J Cancer 90:206–215PubMedCrossRefGoogle Scholar
  37. 37.
    Tanigawa N, Amaya H, Matsumura M, Shimomatsuya T (1997) Correlation between expression of vascular endothelial growth factor and tumor vascularity, and patient outcome in human gastric carcinoma. J Clin Oncol 15:826–832PubMedGoogle Scholar
  38. 38.
    Garden OJ, Rees M, Poston GJ, Mirza D, Saunders M, Ledermann J, Primrose JN, Parks RW (2006) Guidelines for resection of colorectal cancer liver metastases. Gut 55(Suppl 3):iii1–8PubMedCrossRefGoogle Scholar
  39. 39.
    Xavier P, Belo L, Beires J, Rebelo I, Martinez-de-Oliveira J, Lunet N, Barros H (2006) Serum levels of VEGF and TNF-alpha and their association with C-reactive protein in patients with endometriosis. Arch Gynecol Obstet 273:227–231PubMedCrossRefGoogle Scholar
  40. 40.
    Canna K, McArdle PA, McMillan DC, McNicol AM, Smith GW, McKee RF, McArdle CS (2005) The relationship between tumour T-lymphocyte infiltration, the systemic inflammatory response and survival in patients undergoing curative resection for colorectal cancer. Br J Cancer 92:651–654PubMedCrossRefGoogle Scholar
  41. 41.
    Fenwick SW, Toogood GJ, Lodge JP, Hull MA (2003) The effect of the selective cyclooxygenase-2 inhibitor rofecoxib on human colorectal cancer liver metastases. Gastroenterology 125:716–729PubMedCrossRefGoogle Scholar
  42. 42.
    Chalmers CR, Wilson DJ, Ward J, Robinson PJ, Toogood GJ, Hull MA (2006) Antiangiogenic activity of the selective cyclooxygenase-2 inhibitor rofecoxib in human colorectal cancer liver metastases. Gut 55:1058–1059PubMedCrossRefGoogle Scholar
  43. 43.
    Lesterhuis WJ, de Vries IJ, Schuurhuis DH, Boullart AC, Jacobs JF, de Boer AJ, Scharenborg NM, Brouwer HM, van de Rakt MW, Figdor CG, Ruers TJ, Adema GJ, Punt CJ (2006) Vaccination of colorectal cancer patients with CEA-loaded dendritic cells: antigen-specific T cell responses in DTH skin tests. Ann Oncol 17:974–980PubMedCrossRefGoogle Scholar

Copyright information

© Société Internationale de Chirurgie 2008

Authors and Affiliations

  • D. Gomez
    • 1
  • S. Farid
    • 1
  • H. Z. Malik
    • 1
  • A. L. Young
    • 1
  • G. J. Toogood
    • 1
  • J. P. A. Lodge
    • 1
  • K. R. Prasad
    • 1
  1. 1.Hepatobiliary and Transplantation Unit, The Leeds Teaching Hospitals NHS TrustSt. James’s University HospitalLeedsUK

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